People living with HIV/AIDS (PLWHA) suffer increased depression prevalence compared to the general population, which negatively impacts antiretroviral (ART) adherence and HIV-related outcomes leading to morbidity and mortality. Yet depression in this population often goes undiagnosed and untreated. The current project sought to design an evidence-based approach to integrate depression care in HIV clinics. The model chosen, measurement-based care (MBC), is based on existing guidelines and the largest randomized trial of depression treatment. MBC was adapted to clinical realities of HIV care for use in a randomized controlled effectiveness trial of depression management at three academic HIV clinics. The adaptation accounts for drug-drug interactions critical to ongoing ART effectiveness and can be delivered by a multidisciplinary team of nonmental health providers. A treatment algorithm was developed that enables clinically supervised, nonphysician depression care managers (DCMs) to track and monitor antidepressant tolerability and treatment response while supporting nonpsychiatric prescribers with antidepressant choice and dosing. Quality of care is ensured through weekly supervision of DCMs by psychiatrists. Key areas of flexibility that have been important in implementation have included flexibility in timing of assessments, accommodation of divergence between algorithm recommendations and provider decisions, and accommodation of delays in implementing treatment plans. This adaptation of the MBC model to HIV care has accounted for critical antidepressant-antiretroviral interactions and facilitated the provision of quality antidepressant management within the HIV medical home. © 2012 Copyright, Mary Ann Liebert, Inc.